Transcriptional control of myelination and remyelination

Sock, Elisabeth; Wegner, Michael

doi:10.1002/glia.23636

Cited by 84 publications

(64 citation statements)

References 148 publications

(237 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, biosynthesis, storage, and cellular trafficking of myelin lipids are essential to the assembly and maintenance of myelin in the nervous system through life span. Recent reviews have provided updates on the genes, proteins, and molecular signals controlling myelination both in the PNS and CNS [5][6][7]. Herein, we focus on the most recent developments regarding myelin lipids and fatty acids.…”

Section: Introductionmentioning

confidence: 99%

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

241

152

View full text Add to dashboard Cite

Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

show abstract

Section: Introductionmentioning

confidence: 99%

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

241

152

View full text Add to dashboard Cite

show abstract

“…In the OPC cluster, genes implicated in OPC migration ( Cldn11 , Tspan15 ) 13 were upregulated. Genes regulating OPC proliferation and maintenance in the cell cycle were both activated ( Sox4 , Hes5 ) 14 and inhibited ( Id2 , Gpr17 ) 15 . Likewise, genes promoting OPC differentiation and lineage progression were both activated ( Kpna2 , coordinator of transcriptional control of OL differentiation 16 ) and inhibited ( Olig1, Olig2) 15 .…”

Section: Resultsmentioning

confidence: 99%

“…Genes regulating OPC proliferation and maintenance in the cell cycle were both activated ( Sox4 , Hes5 ) 14 and inhibited ( Id2 , Gpr17 ) 15 . Likewise, genes promoting OPC differentiation and lineage progression were both activated ( Kpna2 , coordinator of transcriptional control of OL differentiation 16 ) and inhibited ( Olig1, Olig2) 15 . These results suggest that both OPC recruitment and proliferation and OPC differentiation may be upregulated in distinct subsets of OPCs in response to the fast-refeed paradigm.…”

Section: Resultsmentioning

confidence: 99%

Nutritional signals rapidly activate oligodendrocyte differentiation in the adult hypothalamic median eminence

Kohnke

Lam

Buller

et al. 2019

Preprint

View full text Add to dashboard Cite

The mediobasal hypothalamus (arcuate nucleus - ARC - and median eminence - ME -) controls energy balance, growth and fertility through its ability to integrate neuronal, nutritional and hormonal signals and coordinate the behavioural, neuroendocrine and metabolic responses required for these functions. While our understanding of the neural circuits downstream from ARC neurons is rapidly progressing, little is known about the function of other cell types. Here we describe an unexpected role for oligodendrocytes (OL) of the ME in monitoring nutritional signals. We show that refeeding following an overnight fast rapidly activates oligodendrocyte differentiation and the production of new OL in the ME specifically. No changes in myelination were measured in this time-frame. However, refeeding changed the expression of OL-derived extracellular matrix proteins decorin and tenascin-R, with consistent changes in the density of local perineuronal nets. Last, we show that OLs use mTORC1 signalling, a pathway required for OL differentiation, to survey energy and protein availability, specifically in the ME. We conclude that new oligodendrocytes formed in the ME in response to nutritional signals control the access of circulating metabolic cues to ARC interoceptive neurons.

show abstract

“…Consequently, the mechanisms controlling myelin synthesis, including regulation of the genes encoding myelin related proteins, are the focus of intense investigation (5).…”

Section: Introductionmentioning

confidence: 99%

“…Many of the TFs specifying myelinating cell lineages and/or controlling lineage maturation have been identified (5,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Further, chromatin remodeling and epigenetic changes associated with myelin gene expression have identified numerous features of the chromatin landscape in which such regulatory components operate (33)(34)(35)(36)(37)(38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulators of theGolli/Myelin Basic ProteinLocus Integrate Additive and Stealth Activities

Bagheri

Friedman

Siminovitch

et al. 2020

Preprint

View full text Add to dashboard Cite

Myelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin associated proteins. In the central nervous system (CNS), myelin is elaborated by neuroepithelial derived oligodendrocytes and in the peripheral nervous system (PNS) by neural crest derived Schwann cells.While some myelin proteins are unique to only one lineage, myelin basic protein (Mbp) is expressed in both.Overlapping the Mbp gene is Golli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within the Golli/Mbp locus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to the Golli/Mbp expression program and examine if interactions among these enhancers occur, we derived mouse lines in which enhancers were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of development.Although super-enhancers have been shown to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated functions that were largely additive. However, enhancers demonstrating autonomous activity strictly in one cell lineage, when missing, were found to significantly reduce output in the other thus revealing cryptic "stealth" activity. Further, Golli accumulation in all cell types investigated was markedly and uniformly attenuated by the absence of a key oligodendrocyte enhancer. Our observations expose a novel level of enhancer interaction and are consistent with a model in which enhancermediated DNA looping underlies higher-order Golli/Mbp regulatory organization. AUTHOR SUMMARYThe control of transcription is mediated through regulatory sequences that engage in a lineage and developmentally contextual manner. The Golli/Mbp locus gives rise to several mRNAs and while Mbp mRNAs accumulate exclusively in the two glial cell types that elaborate myelin, Golli mRNAs accumulate in diverse cell types both within and beyond the nervous system. To determine how the different Golli/Mbp enhancers distribute their activities and to reveal if they operate as autonomous agents or have functionally significant interactions with each other we derived multiple enhancer knock-out lines. Comparing the developmental accumulation of Mbp and Golli mRNAs revealed that the autonomous targeting capacity of multiple enhancers accurately predicted their in-situ contributions. Also, they acted in a largely additive manner indicating significant individual autonomy that can be accounted for by a simple chromatin looping model. Unexpectedly, we also uncovered cryptic "stealth" activity emanating from these same enhancers in lineages where they show no autonomous targeting capacity thus providing new insight into the control of lineage specific gene expression.

show abstract

Transcriptional control of myelination and remyelination

Cited by 84 publications

References 148 publications

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Nutritional signals rapidly activate oligodendrocyte differentiation in the adult hypothalamic median eminence

Transcriptional Regulators of theGolli/Myelin Basic ProteinLocus Integrate Additive and Stealth Activities

Contact Info

Product

Resources

About